Ruthenium Complexes
Ruthenium Complexes
Photochemical and Biomedical Applications
Edited by Alvin A. Holder Lothar Lilge Wesley R. Browne Mark A.W. Lawrence Jimmie L. Bullock Jr. Editors All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Prof. Alvin A. Holder editors, and publisher do not warrant the Old Dominion University information contained in these books, Department of Chemistry and including this book, to be free of errors. Biochemistry Readers are advised to keep in mind that 4541 Hampton Blvd. statements, data, illustrations, procedural VA details or other items may inadvertently United States be inaccurate.
Prof. Lothar Lilge Library of Congress Card No.: University of Toronto applied for Princess Margaret Cancer Centre 101 College Street British Library Cataloguing-in-Publication M5G 1L7 ON Data Canada A catalogue record for this book is available from the British Library. Prof. Wesley R. Browne University of Groningen Bibliographic information published by Stratingh Institute of Chemistry the Deutsche Nationalbibliothek Nijenborgh 4 The Deutsche Nationalbibliothek 9747 AG Groningen lists this publication in the Deutsche Netherlands Nationalbibliografie; detailed bibliographic data are available on the Dr. Mark A.W. Lawrence Internet at
Print ISBN: 978-3-527-33957-0 ePDF ISBN: 978-3-527-69520-1 ePub ISBN: 978-3-527-69524-9 Mobi ISBN: 978-3-527-69521-8 oBook ISBN: 978-3-527-69522-5
Cover Design Grafik-Design Schulz, Fußgönheim, Germany Typesetting SPi Global, Chennai, India Printing and Binding
Printed on acid-free paper
10987654321 Dedicated to Karen with admiration, affection, and respect!!
Dear Karen, we will miss you for your class, humour, and knowledge!! Selah R.I.P.
vii
Contents
About the Editors xv Preface xvii Acknowledgments xix
Section I Introduction 1
1 Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon 3 Seth C. Rasmussen 1.1 Introduction 3 1.2 Early Years 4 1.3 Graduate Studies and Clemson University 6 1.4 Postdoctoral Research and the University of California, Berkeley 11 1.5 Washington State University: Beginning an Independent Career 13 1.6 Move to Virginia Tech 15 1.7 Collaboration with Brenda Winkel and the Study of Metal-DNA Interactions 16
1.8 A Return to Where It All Started: Photochemical H2 Production 18 1.9 A Career Cut Tragically Short 19 1.10 Karen’s Legacy 20 Acknowledgments 20 References 20
2 Basic Coordination Chemistry of Ruthenium 25 Mark A. W. Lawrence, Jimmie L. Bullock, and Alvin A. Holder 2.1 Coordination Chemistry of Ruthenium 25 2.1.1 The Element 25 2.1.2 Stereochemistry and Common Oxidation States 26 2.1.2.1 Ruthenium in Low Oxidation States 27 2.1.2.2 Chemistry of Ruthenium(II) and (III) 31 2.1.2.3 Higher Oxidation States of Ruthenium 36 2.1.3 Conclusion 37 References 37 viii Contents
Section II Artificial Photosynthesis 43
3 Water Oxidation Catalysis with Ruthenium 45 Andrea Sartorel 3.1 Introduction 45 3.1.1 Energy Issue and Energy from the Sun 45 3.1.2 Photosynthesis and Solar Fuels 46 3.1.3 Water Oxidation 48 3.1.4 Artificial Water Oxidation 49 3.2 Ruthenium in Water Oxidation Catalyst 50 3.2.1 Ruthenium Oxide 50 3.2.2 Molecular Ruthenium WOC 52 3.2.2.1 Meyer’s Blue Dimer 53 3.2.2.2 The Ru-Hbpp Catalyst 54 3.2.2.3 Single-Site Ru-WOCs 55 3.2.2.4 Heptacoordinated Ru Intermediates 56 3.2.3 Polyoxometalates: The Bridge Between Metal Oxides and Coordination Complexes 57 3.3 Conclusions and Perspectives 60 References 61
4 Ruthenium- and Cobalt-Containing Complexes and Hydrogenases for Hydrogen Production 67 Michael J. Celestine, Raj K. Gurung, and Alvin A. Holder 4.1 Introduction 67 4.2 (A) Ruthenium- and Cobalt-Containing Complexes for Hydrogen Production 68 4.2.1 Nonbridged Systems 68 4.2.2 Bridged Systems 70 4.3 (B) Ruthenium(II)-Containing Complexes and Hydrogenases for Hydrogen Generation in Aqueous Solution 77 4.3.1 Hydrogenases 77 4.3.2 Hydrogenases with Ruthenium(II) Complexes 78 4.4 Conclusions 84 References 85
Section III Applications in Medicine 89
5 Ligand Photosubstitution Reactions with Ruthenium Compounds: Applications in Chemical Biology and Medicinal Chemistry 91 Samantha L. Hopkins and Sylvestre Bonnet 5.1 Introduction 91 5.2 Caging and Uncaging Biologically Active Ligands with a Nontoxic Ruthenium Complex 92 5.3 Caging Cytotoxic Ruthenium Complexes with Organic Ligands 96 Contents ix
5.4 Low-Energy Photosubstitution 100 5.4.1 Introduction 100 5.4.2 Modulating Ru Photophysics by Ligand Modulation 100 5.4.3 Upconversion (UC) 105 5.4.3.1 Triplet–Triplet Annihilation Upconversion 105 5.4.3.2 Upconverting Nanoparticles (UCNPs) 106 5.4.3.3 Two-Photon Absorption (TPA) Photosubstitution 109 5.5 Conclusions 110 References 111
6 Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy 117 Lothar Lilge 6.1 Introduction 117 6.2 The Basics of Photodynamic Therapy 118 6.2.1 Singlet Oxygen Production 120 6.2.2 Other Radical Production 120 6.2.3 PDT Dose Definition 120 6.2.3.1 PDT Dosimetry In Vitro 122 6.2.3.2 PDT Dosimetry In Vivo 124 6.2.3.3 Oxygen Consumption Model 125 6.2.3.4 In Vivo Tissue Response Models 125 6.2.4 PDT and Immunology 126 6.3 Status of Ru Photosensitizing Complexes 126 6.3.1 Photostability for Ru-PS Complexes 128 6.3.2 Long Wavelength Activation of Ru(II)-PS Complexes 128 6.4 Issues to Be Considered to Further Develop Ru-Based Photosensitizers 129 6.4.1 Subcellular Localization 130 6.4.2 Ruthenium Complex Photosensitizers and the Immune Response 131 6.5 Future Directions for Ru-PS Research 131 6.6 Conclusion 132 References 132
7 Photodynamic Therapy in Medicine with Mixed-Metal/Supramolecular Complexes 139 Jimmie L. Bullock and Alvin A. Holder 7.1 Introduction 139 7.2 Platinum and Rhodium Centers as Bioactive Sites 140 7.2.1 Platinum(II)-Based Chemotherapeutics 140 7.2.2 Rhodium(III) as a Bioactive Site 141 7.3 Supramolecular Complexes as DNA Photomodification Agents 142 7.4 Mixed-Metal Complexes as Photodynamic Therapeutic Agents 143 7.4.1 Photosensitizers with a Ru(II) Metal Center Coupled to Pt(II) Bioactive Sites 143 x Contents
7.4.1.1 Binuclear Complexes with Ru(II) and Pt(II) Metal Centers with Bidentate Ligands 143 7.4.1.2 Binuclear and Trinuclear Complexes with Ru, Pt with Tridentate Ligands 146 7.4.2 Photosensitizers with a Ru(II) Metal Center Coupled to Rh(III) Bioactive Sites 147 7.4.2.1 Trinuclear Complexes with Ru(II), Rh(III), and Ru(II) Metal Centers 147 7.4.2.2 Binuclear Complexes with Ru(II) and Rh(III) Metal Centers 149 7.4.3 Photosensitizers with a Ru(II) Metal Cenetr Coupled to Other Bioactive Sites 150 7.4.3.1 Binuclear Complexes with Ru(II) and Cu 150 7.4.3.2 Binuclear Complexes with Ru(II) and Co(III) Metal Centers 151 7.4.3.3 Binuclear Complexes with Ru (II) and V(IV) Metal Centers 151 7.4.3.4 Applications of Ru(II) Metal Centers in Nanomedicine 152 7.5 Summary and Conclusions 155 Abbreviations 156 References 157
8 Ruthenium Anticancer Agents En Route to the Tumor: From Plasma Protein Binding Agents to Targeted Delivery 161 Muhammad Hanif and Christian G. Hartinger 8.1 Introduction 161 8.2 Protein Binding RuIII Anticancer Drug Candidates 163 8.2.1 RuIII Anticancer Drug Candidates Targeting Primary Tumors 163 8.2.2 Antimetastatic RuIII Compounds 165 8.3 Functionalization of Macromolecular Carrier Systems with Ru Anticancer Agents 166 8.3.1 Proteins as Delivery Vectors for Organometallic Compounds 166 8.3.2 Polymers and Liposomes as Delivery Systems for Bioactive Ruthenium Complexes 168 8.3.3 Dendrimers 169 8.4 Hormones, Vitamins, and Sugars: Ruthenium Complexes Targeting Small Molecule Receptors 169 8.5 Peptides as Transporters for Ruthenium Complexes into Tumor Cells and Cell Compartments 173 8.6 Polynuclear Ruthenium Complexes for the Delivery of a Cytotoxic Payload 174 8.7 Summary and Conclusions 175 Acknowledgments 175 References 176
9 Design Aspects of Ruthenium Complexes as DNA Probes and Therapeutic Agents 181 Madeleine De Beer and Shawn Swavey 9.1 Introduction 181 9.2 Physical Interaction to Disrupt DNA Structure 181 Contents xi
9.2.1 Irreversible Covalent Binding 182 9.2.2 Intercalation 184 9.2.3 Additional Noncovalent Binding Interactions 185 9.3 Biological Consequences of Ru-Complex/DNA Interactions 186 9.4 Effects of Ru Complexes on Topoisomerases and Telomerase 191 9.5 Summary and Conclusions 196 References 197
10 Ruthenium-Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action 201 António Matos, Filipa Mendes, Andreia Valente, Tânia Morais, Ana Isabel Tomaz, Philippe Zinck, Maria Helena Garcia, Manuel Bicho, and Fernanda Marques 10.1 Introduction 201 10.2 Cellular Uptake 204 10.3 DNA and DNA-Related Cellular Targets 205 10.4 Targeting Signaling Pathways 207 10.5 Targeting Enzymes of Specific Cell Functions 207 10.6 Targeting Glycolytic Pathways 209 10.7 Macromolecular Ruthenium Conjugates: A New Approach to Targeting 211 10.8 Conclusions 214 References 215
11 Targeting cellular DNA with Luminescent Ruthenium(II) Polypyridyl Complexes 221 Martin R. Gill and Jim A. Thomas 11.1 Introduction 221 11.1.1 DNA-Binding Modes of Small Molecules 222 11.1.2 Metal Complexes and DNA 223 2+ 11.2 [Ru(bpy)2(dppz)] and the DNA “Light-Switch” Effect 224 11.3 Cellular Uptake of RPCs and Application as DNA-Imaging Agents 226 11.3.1 Mononuclear Complexes 226 11.3.2 Dinuclear Complexes 228 11.3.3 Cyclometalated Systems 228 11.4 Alternative Techniques to Assess Cellular Uptake and Localization 231 11.5 Toward Theranostics: luminescent RPCs as Anticancer Therapeutics 232 11.6 Summary and Conclusions 234 References 235
12 Biological Activity of Ruthenium Complexes With Quinoline Antibacterial and Antimalarial Drugs 239 Jakob Kljun and Iztok Turel 12.1 Introduction 239 xii Contents
12.2 Antibacterial (Fluoro)quinolones 240 12.2.1 Quinolones and Their Interactions with Metal Ions 241 12.2.2 Ruthenium and Quinolones 241 12.2.3 Ruthenium and HIV Integrase Inhibitor Elvitegravir 245 12.3 Antibacterial 8-Hydroxyquinolines 246 12.3.1 Mode of Action of 8-Hydroxyquinoline Agents 246 12.3.2 Ruthenium and 8-Hydroxyquinolines 247 12.4 Antimalarial 4-Aminoquinolines 248 12.4.1 Mechanism of Action of Antimalarial Quinoline Agents 248 12.5 Metallocene Analogues of Chloroquine 249 12.6 Conclusions 252 References 252
13 Ruthenium Complexes as NO Donors: Perspectives and Photobiological Applications 257 Loyanne C.B. Ramos, Juliana C. Biazzotto, Juliana A. Uzuelli, Renata G. de Lima, and Roberto S. da Silva 13.1 Introduction 257 13.2 Photochemical Processes of Some Nitrogen Oxide Derivative–Ruthenium Complexes 258 13.2.1 Metal-Ligand Charge-Transfer Photolysis of {Ru-NO}6 258 13.2.2 Nitrosyl Ruthenium Complexes: Visible-Light Stimulation 261 13.3 Photobiological Applications of Nitrogen Oxide Compounds 265 13.3.1 Photovasorelaxation 265 References 268
14 Trends and Perspectives of Ruthenium Anticancer Compounds (Non-PDT) 271 Michael A. Jakupec, Wolfgang Kandioller, Beatrix Schoenhacker-Alte, Robert Trondl, Walter Berger, and Bernhard K. Keppler 14.1 Introduction 271 14.2 Ruthenium(III) Compounds 272 14.2.1 NAMI-A 273 14.2.1.1 Biotransformation 273 14.2.1.2 Antimetastatic Activity 274 14.2.1.3 Mode of Action 274 14.2.1.4 Clinical Studies and Perspectives 275 14.2.2 KP1019/NKP-1339 276 14.2.2.1 Tumor Targeting Mediated by Plasma Proteins 276 14.2.2.2 Activation by Reduction 277 14.2.2.3 Mode of Action 278 14.2.2.4 Clinical Studies and Perspectives 281 14.3 Organoruthenium(II) Compounds 282 14.3.1 Ruthenium(II)–Arene Compounds in Preclinical Development 282 14.3.1.1 Organoruthenium Complexes Bearing Bioactive Ligand Scaffolds 284 Contents xiii
14.3.1.2 Cytotoxic Organoruthenium Complexes without Activation by Aquation 285 References 286
15 Ruthenium Complexes as Antifungal Agents 293 Claudio L. Donnici, Maria H. Araujo, and Maria A. R. Stoianoff 15.1 Introduction 293 15.2 Antifungal Activity Investigations of Ruthenium Complexes 304 15.2.1 Ruthenium Complexes with Activity against Several Pathogenic Fungi Species: Dinuclear, Trinuclear, and Tetranuclear ruthenium Polydentate Polypyridil ligands, Heterotrimetallic di-Ruthenium-Mono-Palladium Complexes, Dinuclear bis-β-Diketones and Pentadithiocarbamate Ligands 304 15.2.2 Aromatic and Heteroaromatic Ligands in Ru Monometallic Centers (Pyridine, Phenantroline, Terpyridine, Quinoline, and Phenazine) 305 15.2.3 Schiff bases, Thiosemicarbazones, and Chalcones 307 15.2.3.1 Schiff bases (Tetradentate Salen Like, Tridentate, and bidentate) 307 15.2.3.2 Thiosemicarbazones 309 15.2.3.3 Chalcone Derivatives 310 15.2.4 Other ligands (Dithio-Naphtyl-Benzamide, Arylazo, Catecholamine, Organophosphorated, Hydridotris(pyrazolyl)borate and Bioactive Azole Ligands) 310 15.3 Conclusion 312 References 313
Index 319
xv
About the Editors
Alvin A. Holder is an associate professor at Old Dominion University in Norfolk, USA. He graduated from the University of the West Indies (UWI), Mona Campus, Jamaica, with a BSc (special chemistry) in 1989 and acquired his PhD in inorganic chemistry in 1994 with Prof. Tara P. Dasgupta. He was a faculty member at the University of the West Indies, Cave Hill Campus, Barbados, and an assistant pro- fessor in chemistry at the University of Southern Mississippi. His current research involves transition metal chemistry and he has published more than 65 articles and several textbooks and book chapters. In 2012, he was awarded an NSF Career Award. Lothar Lilge is a Senior Scientist at the Princess Margaret Cancer Centre and holds a professorship at the University of Toronto, Canada. He obtained his Diploma in physics from the Johann Wolfgang Goethe University in Frankfurt, Germany, and his PhD in biophysics from the Westfaehlische Wilhelms Uni- versity in Muenster, Germany. Additional training was provided through the Wellman Laboratories of Photomedicine at Massachusetts General Hospital, Boston, USA, and during a post-doc at McMaster University in Hamilton, Canada. His work is focused on photodynamic therapy including the use of ruthenium-based photosensitizers and optical spectroscopy for diagnostic and risk assessment among a range of other biophotonic application in medicine. Wesley R. Browne is an associate professor at Stratingh Institute for Chemistry at the University of Groningen, The Netherlands, since 2013. He completed his PhD at Dublin City University, Ireland, with Prof. J. G. Vos in 2002, followed by a post-doc under the joint guidance of Prof. J. G. Vos and Prof. J. J. McGarvey, Queens University Belfast, UK. Between 2003 and 2007 he was a postdoc- toral research fellow in the group of Prof. B. L. Feringa at the University of Groningen. He was appointed assistant professor in 2008. His current research interests include transition-metal-based oxidation catalysis, electrochromic materials, and responsive surfaces. He is an advisory board member for the European Journal of Inorganic Chemistry, Particle & Particle Characterization (both Wiley) and Chemical Communications (RSC). He has (co-)authored over 150 research papers, reviews, and book chapters. Mark A. W. Lawrence was a post-doctoral fellow at Old Dominion University in Norfolk, USA, in the group of Prof. A. Holder. He received his BSc degree in 2006 xvi About the Editors
and his PhD degree in inorganic-physical chemistry in 2011 from the University of the West Indies (UWI), Mona Campus, Jamaica, with Prof. Tara P. Dasgupta. His research interests include synthesis of hydrazones and functionalized pyridyl benzothiazoles, their transition metal complexes and application to catalysis and biological processes. Jimmie L. Bullock Jr is a PhD student at the University of Kentucky in Lexington, USA, in the department of Chemistry. He received his BSc from Longwood University, Farmville, USA, and his MS in biological inorganic chemistry from Old Dominion University, Norfolk, USA, in 2013 and 2016, respectively. His research interests include studying activation of signaling pathways induced by non-platinum-based chemotherapeutic agents and synthesis of lanthanide sensor molecules. xvii
Preface
Ruthenium, a second-row transition metal, continues to attract much attention in scientific research, as it possesses a vast array of novel applications and proper- ties. The enormous chemistry of ruthenium, much of which remains untapped, has been and continues to be investigated by numerous researchers. One such person was an icon, Prof. Karen J. Brewer. Karen, as she was affectionately called by many of her friends and research students, is being honored for her contribu- tion to research on ruthenium with this textbook. Ruthenium and its compounds are also paramount in catalysis and medicine, so it is not surprising that its biological activities and coordination chemistry remain very active areas of research. Ruthenium-containing complexes have long been known to be well suited for biological applications, and have long been studied as replacements to popular platinum-based drugs. The textbook entitled “Ruthenium Complexes: Photochemical and Biomedical Applications” focuses on the uses and application of ruthenium-containing complexes in medicine and renewable energy. This title is unique as it discusses potential applications of ruthenium complexes in solving some of the world’s foremost problems. While the biological application of ruthenium-containing complexes has been known for years, their application as photosensitizers in the emerging field of photodynamic therapy, also known as photochemotherapy, is of special interest. Photodynamic therapy can be utilized to treat a wide range of medical conditions including macular degeneration and malignant cancers. Ruthenium-containing photosensitizers have been shown to be espe- cially active in the latter, with often minimal dark toxicity. Light-activated ruthenium-containing complexes are also gaining much attention as molecular catalysts in artificial photosynthesis for the production of hydrogen gas in aqueous media, after water oxidation. Our goal at the outset was to capture the full vibrancy of the biological and coordination chemistry of this very important element called ruthenium and, in this way, to reflect the insight and enthusiasm of the honoree, Karen. To do so, we have divided this textbook into three sections with 15 chapters: (1) Intro- duction (Chapters 1–2), (2) Artificial Photosynthesis (Chapters 3 and 4), and (3) Applications in Medicine (Chapters 5–15). As such, we invited experts in each of these areas to complete this project by contributing a chapter. The chapters are as follows: Chapter 1: Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon; Chapter 2: Basic Coordination Chemistry of Ruthenium; xviii Preface
Chapter 3: Water Oxidation Catalysis with Ruthenium; Chapter 4: Ruthenium- and Cobalt-Containing Complexes and Hydrogenases for Hydrogen Production; Chapter 5: Ligand Photosubstitution Reactions with Ruthenium Compounds: Applications in Chemical Biology and Medicinal Chemistry; Chapter 6: Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy; Chapter 7: Photodynamic Therapy in Medicine with Mixed-Metal/Supramolecular Complexes; Chapter 8: Ruthenium Anticancer Agents En Route to the Tumor: From Plasma Protein Binding Agents to Targeted Delivery; Chapter 9: Design Aspects of Ruthenium Complexes as DNA Probes and Therapeutic Agents; Chapter 10: Ruthenium-Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action; Chapter 11: Targeting cellular DNA with Luminescent Ruthenium(II) Polypyridyl Complexes; Chapter 12: Biological Activity of Ruthenium Complexes With Quinoline Antibacterial and Antimalarial Drugs; Chapter 13: Ruthenium Complexes as NO Donors: Perspec- tives and Photobiological Applications; Chapter 14: Trends and Perspectives of Ruthenium Anticancer Compounds (Non-PDT); and Chapter 15: Ruthenium Complexes as Antifungal Agents. It has been our good fortune to work with so many exceptionally talented contributors from all over the world in compiling a textbook that we believe will be a valuable resource for graduate students, young investigators, and more senior scholars in the field of biological and coordination chemistry. We thank all the contributors for their hard work and their willingness to assist us whenever requested.
July 20, 2017 Alvin Holder Co-Editor Norfolk, Virginia, USA xix
Acknowledgments
This is my acknowledgment which is based on the influence of Professor Karen Brewer on my life as she taught me how to carry out good and sensible chemistry with osmium(II), ruthenium(II), and rhodium(III) complexes. Photodynamic therapeutic studies with pUC18 and pBluescript DNA plasmids and Vero cells were the order of the day! This research catalyzed my career and research in the USA. The task of working with so many gifted authors has been a real treat for me. The project also presented many challenges. We would not have made it tothe finish line without the assistance of so many colleagues. We have not lost any Soldados on this journey. Thank God!! In an Invited Plenary Talk: 251st ACS National Meeting and Exposition, March 13–17, 2016, San Diego, California. Abstract # INOR-1141. Title: “Light that pleases the world in science: The Karen Brewer’s effect on my academic career.” Author: AlvinA.Holder; I learnt about the seven (7) Ps from Professor Mark Richter and the Brew Crew, who attended the ACS conference. They are as follows: The seven (7) Ps Proper Prior Planning Prevents Piss Poor Performance Creditfortheseven(7)Psmustbegiventomydeceasedformerpostdoctoral mentor, Professor Karen J. Brewer. She was a great Lady, who believed in “Family First”!! Please see http://www.chem.vt.edu/media/karen-brewer-obituary.pdf. R.I.P. I would like to thank the National Science Foundation (NSF) for a National Science Foundation CAREER Award as this material is based upon work supported by the National Science Foundation under CHE-1431172 (formerly CHE – 1151832). I would also like to thank Old Dominion University’s Faculty Proposal Preparation Program (FP3), and also for the Old Dominion University start-up package that allowed for the successful completion of this work. Full xx Acknowledgments
gratitude to Professor Karen Brewer (R.I.P.), Professor Brenda Winkel, Professor Larry Taylor, Dr Myra Gordon, the research group (The Brew Crew), and all at Virginia Tech. Personally, I would like to thank Dr. Anne Brennführer, Dr. Eva-Stina Müller, Ramprasad Jayakumar, Anne, Claudia Nussbeck, Dr. Eva-Stina Müller, and Samnaa Srinivas.
Alvin A. Holder Co-Editor 1
Section I
Introduction
3
1
Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon Seth C. Rasmussen
North Dakota State University, Department of Chemistry and Biochemistry, Fargo, ND 58108-6050, USA
1.1 Introduction
Over the span of her career, first at Washington State University (WSU) and later at Virginia Tech, Karen J. Brewer (Figure 1.1) earned international acclaim as a prolific and pioneering researcher in the photochemistry and photophysics of multimetallic complexes [1, 2]. Ranging from synthesis of new multimetallic complexes to the study of their ground- and excited-state properties, her contributions aimed to elucidate the effect of the specific assembly of such complexes on their respective spectroscopic and electrochemical properties. In the process, Karen studied the application of complexes to molecular photovoltaics, solar H2 production, artificial photosynthesis, electrocatalysis, Pt-based DNA binders, and photodynamic therapy [1–6]. Publishing her first paper in 1985, she accumulated over 125 peer-reviewed research publications in her career, which have in turn garnered over 3000 citations to date [1, 2], and her research pace was as active as ever at the time of her premature death in 2014 (Figure 1.2) [1].
Figure 1.1 Karen J. Brewer (1961–2014) in the Spring of 2014. (Courtesy of Virginia Tech.)
Ruthenium Complexes: Photochemical and Biomedical Applications, First Edition. Edited by Alvin A. Holder, Lothar Lilge, Wesley R. Browne, Mark A.W. Lawrence, and Jimmie L. Bullock Jr. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 4 1 Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon
8
6
4 Publications 2
0 1985 1990 1995 2000 2005 2010 2015 Year
Figure 1.2 Publications per year from 1985 to 2015. Although known specifically for her various research contributions, Karen was also an award-recognized educator. She was comfortable teaching chemistry at all levels, from first-year students in general chemistry to graduate students in special topics classes such as electrochemistry and the photophysics of transi- tion metal complexes. Her enthusiasm in the classroom was infectious and she inspired students to change not only their view of chemistry but, in some cases, their major to chemistry [1]. For many, including this author, Karen will be remembered most for her role as mentor and role model. She had tremendous impact on everyone who transitioned through her research laboratory, from undergraduates to postdocs. Throughout her career, Karen was a strong advocate for women and minorities in chemistry and was a role model and mentor for many female students and researchers [1, 2, 5]. Her passion in the promotion of chemistry as a career choice for women was most evident in her extensive outreach efforts to K-12 students. Throughout her career, she regularly visited primary and secondary school classrooms and hosted students in her laboratories at Virginia Tech [1, 2, 5]. In the process, Karen provided a real-life role model for young girls and others with aspirations to work in the physical sciences [1, 5]. Over the years, Karen received significant recognition for her collective efforts in research, teaching, and outreach. This included a College of Arts and Sciences Diversity Award in 1996, shortly after arriving at Virginia Tech [1, 5], as well as various teaching awards [3] and a Popular Mechanics Breakthrough Innovator Award in 2010, which she shared with collaborator Dr Brenda Winkel [2–5]. Most recently, Virginia Tech recognized her outreach efforts with the 2014 Alumni Award for Outreach Excellence [1–4], which she shared with Dr Shamindri Arachchige, Virginia Tech instructor of chemistry and a former postdoctoral researcher from her research group [1, 5, 7].
1.2 Early Years
Karen Sonja Jenks was born on June 27, 1961, in Wiesbaden, Germany to parents Gerda and Henry Jenks [3, 4]. As the daughter of a career military man, 1.2 Early Years 5
Figure 1.3 Karen in kindergarten at age 5. (Courtesy of Elise Naughton and the Brewer family.)
Karen moved frequently in her youth (Figure 1.3) [2–4], which provided her the opportunity to see much of the United States and the world as a young girl [3, 4]. The family ultimately settled in Lancaster, South Carolina in 1974, where Karen graduated with honors from Lancaster High School in 1979 (Figure 1.4) [3, 4]. Karen then attended Wofford College in Spartanburg, South Carolina [2–4, 6] on a Reserve Officers’ Training Corps (ROTC) scholarship [8]. It was an interest- ing time to attend Wofford College, as it had formerly been an all-male school and had transitioned to a coeducational institution only 3 years before she began her studies there [8]. Karen soon decided that the military was not what she wanted to do with her career and enrolled in Wofford’s K-12 education program, where she was involved in teacher training at the middle school level [8]. Her father had instilled a love of learning and teaching [8] and this probably influenced her decision. Ultimately, however, she developed an interest in chemistry and she finished her undergraduate studies in the chemistry program. While at Wofford she also participated in women’s basketball and became a member of both Alpha Phi Omega and the American Chemical Society during her senior year [2, 6]. The Wofford chemistry faculty thought highly of Karen as a student [9] and she received her BS degree in chemistry in 1983 [2–4, 6]. After the completion of her undergraduate studies, she married Ralph Gary Brewer (who went by Gary), with 6 1 Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon
Figure 1.4 Karen in her senior year of high school at age 17. (Courtesy of Elise Naughton and the Brewer family.)
their wedding held on the same day as their Wofford graduation ceremonies on Sunday, May 15, 1983. Following her marriage, Karen was known both personally and professionally as Karen Jenks Brewer.
1.3 Graduate Studies and Clemson University
KarenthenenteredtheChemistrygraduateprogramatClemsonUniversity in the fall of 1983, where she began working under the supervision of Dr John D. Petersen (b. 1947, PhD University of California, Santa Barbara 1975) (Figures 1.5 and 1.6). Notable coworkers during her time in the Petersen group included Ronald Ruminski (Professor, University of Colorado Colorado Springs; PhD University of New Mexico 1980; Petersen postdoc 1981–1984) [10], Wyatt Rorer Murphy, Jr (Professor, Seton Hall University; PhD University of North Carolina at Chapel Hill 1984; Petersen postdoc 1984–1986) [11], and D. Brent MacQueen (PhD Clemson 1989) [12]. Karen began her research in the Petersen laboratory by joining ongoing efforts to develop bimetallic complexes capable of converting radiation to usable chemical potential energy. The basic design of such species included 1.3 Graduate Studies and Clemson University 7
Figure 1.5 John D. Petersen (b. 1947). (Courtesy of John Petersen.) three components (Figure 1.5): (i) a strongly absorbing, but photochemically unreactive, metal center (antenna complex); (ii) a second metal center capable of undergoing a useful chemical reaction from a nonspectroscopic excited state (reactive complex); and (iii) a bridging ligand (BL) that both couples the two metal fragments and facilitates intramolecular energy transfer between the two metal centers [12, 13]. While others had previously studied electron transfer in bimetallic complexes utilizing primarily monodentate BLs (Figure 1.7), the Petersen group focused on the application of bidentate BLs (Figure 1.8) as a method to increase stability of the bimetallic species during excitation. Karen’s first publication was as fourth author on a 1985 paper published in Coordination Chemistry Reviews that presented this design and discussed the optimization of the three basic components [13]. Karen’s research initially focused on evaluating the effect of bidentate BLs such as dpp on the photophysics of Ru(II)-based antenna complexes. This resulted in the publication of her initial first-author paper in 1986, which reported the 2+ synthesis of [Ru(dpp)3] along with its photophysical and electrochemical prop- 2+ erties [14]. The conclusion of this work was that in comparison to [Ru(bpy)3] , the dpp analogue exhibited similar electronic absorption and emission spectra, as well as a similar luminescence quantum yield. As such, the application of dpp should allow the tethering of Ru(II)-based antenna complexes of reactive metal centers without the loss of the desired photophysical properties [12, 14]. The ultimate focus of the majority of her graduate work was the potential application of bimetallic complexes to the photochemical elimination of molecular hydrogen. These efforts began with an intermolecular sensiti- zation study using Fe(bpy)2(CN)2 as the donor and the dihydride species [Co(bpy)(PEt2Ph)2H2]ClO4 in order to evaluate the relative energy levels of the visible light accessible excited state of the Fe(II) antenna and the reactive 8 1 Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon
Pelope
Nicolo da Lonigo Christophle Glaser MD/PhD Padua 1453 MD Basel ~1640 Antonio Musa Brasavola Nicolas Lemery MD/PhD Ferrara 1520 Apothecary Paris ~1667 Gabriele Fallopio J. G. Spitzley MD Ferrara 1548 Apothecary Paris Girolamo Fabrici Guillaume Francois Roulle MD Padua 1559 Apothecary Paris 1725 Giulio Cesare Casseri MD Padua 1580 From Tingry Antoine Laurent Lavoiser Adriaan van den Spieghel LLB Paris 1764 Pierre Joseph Macquer MD Padua ~1603 MD Paris 1742 Werner Rolfinck Jean Baptiste Michel Bucquet MD Padua 1625 MD Paris 1770 Georg Wolfgang Wedel Claude Louis Berthollet MD Jena 1669 MD Paris 1778 Johann Adolph Wedel MD Jena 1697 Johann Friedrich Wilhelm de Charpentier Leipzig ~1766 Georg Erhardt Hamberger Christian Hieronymus MD Jena 1721 Lömmer Christoph Andreas Mangold MD Erfurt 1751 Johann Gottfried Schreiber MD Glasgow 1740 Ernst Gottfried Baldinger MD Jena 1760 Joseph Louis Gay-Lussac MA Paris 1800 Johann Christian Wiegleb Pierre Berthier Ing. Ord. Ecole des Mines 1805 Apothecary Langensalza ~1765 Johann Friedrich August Göttling To Roulle Apothecary Langensalza 1775 Arnot Justus von Liebig Pierre Francois Tingry John Allen PhD Erlangen 1822 Paris ~1770 MD Edinburgh 1791 August Wilhelm von Hofmann Augustin LeRoyer Charles Gaspard De La Rive PhD Giessen 1841 Geneva MD Edinburgh 1797 Karl Friedrich von Auwers Jean Baptiste Andre Dumas Henri Victor Regnault PhD Berlin 1885 Geneva ~1823 PhD Paris 1837 Josiah Parsons Cooke Jocelyn Field Thorpe AB Harvard 1848 PhD Heidelberg 1895
Theodore William Richards George Armand Robert Kon PhD Harvard 1888 DSc Imperial College 1922
Gilbert Newton Lewis Reginald Patrick Linstead PhD Harvard 1899 PhD Imperial College 1926 William von Eggers Doering Axel Ragnar Olson PhD Berkeley 1917 PhD Harvard 1943 Kenneth Berle Wiberg George Glockler PhD Columbia 1950 PhD Berkeley 1923 Peter Campbell Ford Melvin Calvin PhD Yale 1966 PhD Berkeley 1935 Legend John David Petersen PhD UC Santa Barbara 1975 Primary Influence
Secondary Influence Karen Jenks Brewer © 2016 Seth C. Rasmussen PhD Clemson 1987
Figure 1.6 Karen Brewer’s academic genealogy.